With the aim of determining genetic and epidemiological factors in age-related traits, we are applying new statistical approaches to look for covariates and hidden correlations in large population data sets. A particular focus is the NIA-sponsored study of the "founder" Sardinian population, where inter-relatedness and stable environment of the population over many generations can simplify the analysis. In the first two years of a projected 5-year contract, the group of Dr. G. Pilia has recruited 4,300 subjects, (about 40% of the population in a targeted region of 4 towns in Sardinia), including several thousand sib pairs and many nuclear family units reflecting the entire population age range from 14 years up. For each subject, a database records medical and family history, a questionnaire to assess personality characteristics, a series of blood tests that include measures of heart disease risk factors (cholesterol, fasting lipoprotein levels, etc.), and experimental measures of pulse wave velocity and carotid artery intima-medial thickness. The distribution of values for each quantitated trait has been measured by collaborating investigators (?other NIH participants? above), and systematic studies of heritability have been initiated. The first analyses show that 1) variance for individual traits in the population is similar to that in other, outbred populations studied, though some factors (like the levels of HDL) show distinctive differences in the mean of the population distribution; and 2) in general, the levels of heritability for a wide variety of traits are sufficient to detect genetic loci that account for about 5% of the variance. While further population recruitment and whole-genome scans of the population begin to search for genes involved in the determination of particular traits, targeted data analysis is being done in this subproject with 3 ongoing aims: first, looking for correlated/overlapping genetic and epidemiological factors, and comparing possible correlations with other large population cohort studies, including the Baltimore Longitudinal Study of Aging; second, optimizing heritability in the Sardinian study with combinations of traits; and third, using the knowledge of family relationships to assess the fraction of "heritability" selectively attributable to genetic vs. epidemiological factors.